Cytotoxic activity of 2 ',2 '-difluorodeoxycytidine (gemcitabine) in poorly differentiated thyroid carcinoma cells

Poorly differentiated and anaplastic thyroid cancers are aggressive and usu ally fatal neoplasms, despite aggressive treatment. We performed an in vitr o study to assess the activity of gemcitabine (2',2' difluorodeoxy-cytidine ), a new fluorinated nucleoside analogue, against three poorly differentiat ed human thyroid carcinoma cell lines (ARO, WRO, and NPA). Each cell line w as exposed to increasing concentrations of gemcitabine (0.0003 to 3000 mu m ol/L) for 24, 48, and 72 hours. Maximal reduction in cell viability was see n after 72 hours of gemcitabine for all three cell lines as measured by 3-( 4,5-dimethyl thiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) assay. NPA cells were more sensitive than the other two lines after 24 and 48 hours o f exposure, but all cell lines were similarly sensitive at 72 hours. A cyto toxic effect was confirmed by DNA assay of adherent cells. IC50 concentrati ons for reduction in cell viability ranged from 0.731 and 0.986 mu mol/L fo r each cell line after 72 hours of exposure. These concentrations are lower than serum levels in phase 1 clinical trials of gemcitabine for other mali gnancies. In summary, gemcitabine has activity against poorly differentiate d thyroid cancer cell lines in vitro. In vivo studies using xenograft model s are warranted to confirm these promising observations.